Biomarkers for anti‑vascular endothelial growth factor drugs

Kuriyama,Sho; Yamada,Takeshi; Matsuda,Akihisa; Takahashi,Goro; Iwai,Takuma; Takeda,Kohki; Ueda,Koji; Miyasaka,Toshimitsu; Yokoyama,Yasuyuki; Shinji,Seiichi; Sonoda,Hiromichi; Ohta,Ryo; Yonaga,Kazuhide; Kanaka,Shintaro; Yoshida,Hiroshi

doi:10.3892/ol.2022.13583

Biomarkers for anti‑vascular endothelial growth factor drugs

Authors:
- Sho Kuriyama
- Takeshi Yamada
- Akihisa Matsuda
- Goro Takahashi
- Takuma Iwai
- Kohki Takeda
- Koji Ueda
- Toshimitsu Miyasaka
- Yasuyuki Yokoyama
- Seiichi Shinji
- Hiromichi Sonoda
- Ryo Ohta
- Kazuhide Yonaga
- Shintaro Kanaka
- Hiroshi Yoshida
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Affiliations: Department of Gastrointestinal and Hepato‑Biliary‑Pancreatic Surgery, Nippon Medical School, Tokyo 113‑8603, Japan, Department of Digestive Surgery, Nippon Medical School Musashikosugi Hospital, Kawasaki, Kanagawa 211‑8533, Japan
Published online on: November 7, 2022 https://doi.org/10.3892/ol.2022.13583
Article Number: 463
Copyright: © Kuriyama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Angiogenesis is regulated by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors. VEGF‑A, VEGF‑D, placental growth factor (PlGF) and plasminogen activator inhibitor‑1 (PAI‑1) have tumor angiogenic activity. VEGF‑A and PAI‑1 levels in the blood may impact the activity of bevacizumab, and VEGF‑D levels may similarly diminish the efficacy of ramucirumab. However, the dynamics of these angiogenic biomarkers for anti‑VEGF therapy have not been well established; therefore, they were evaluated in this retrospective study, which included two cohorts. Cohort 1 included patients who were treated with cytotoxic agents and bevacizumab as first‑line chemotherapy, and Cohort 2 comprised patients who were treated with cytotoxic agents and anti‑VEGF drugs (bevacizumab, ramucirumab or aflibercept) as second‑line chemotherapy. VEGF‑A, VEGF‑D, PlGF and PAI‑1 levels were measured before starting chemotherapy and were re‑assessed every 1‑2 months until disease progression. Bevacizumab had reduced benefit as a first‑line chemotherapeutant in patients with very low or very high levels of VEGF‑A. Bevacizumab increased VEGF‑A and PlGF levels, but not VEGF‑D or PAI‑1. Anti‑VEGF drugs offered the greatest benefit to patients with high PAI‑1 before first‑ and second‑line chemotherapy. PAI‑1 levels were not affected by anti‑VEGF drugs. Since ramucirumab increased VEGF‑D, it offered less benefit to patients with high VEGF‑D in second‑line chemotherapy. Conversely, aflibercept offered greater benefits to patients with high VEGF‑D, without increasing VEGF‑D. These biomarkers may be useful for the prediction of drug efficacy and may predict resistance to anti‑VEGF drugs.

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